The bifunctional protein hldE includes D-glycero-beta-D-manno-heptose-7-phosphate kinase and D-glycero-beta-D-manno-heptose 1-phosphate adenylyltransferase activity (cf. EC 2.7.7.70). The enzyme is involved in biosynthesis of ADP-L-glycero-beta-D-manno-heptose, which is utilized for assembly of the lipopolysaccharide inner core in Gram-negative bacteria. The enzyme selectively produces D-glycero-beta-D-manno-heptose 1,7-bisphosphate .
Specify your search results
The expected taxonomic range for this enzyme is: Bacteria, Archaea, Eukaryota
The bifunctional protein hldE includes D-glycero-beta-D-manno-heptose-7-phosphate kinase and D-glycero-beta-D-manno-heptose 1-phosphate adenylyltransferase activity (cf. EC 2.7.7.70). The enzyme is involved in biosynthesis of ADP-L-glycero-beta-D-manno-heptose, which is utilized for assembly of the lipopolysaccharide inner core in Gram-negative bacteria. The enzyme selectively produces D-glycero-beta-D-manno-heptose 1,7-bisphosphate [5].
bifunctional D-beta-D-heptose-7-phosphate kinase/D-beta-D-heptose-1-phosphate adenylyltransferase. Based on genomic sequence comparisons, bifunctional proteins are predicted to be present in several Gram-negative microorganisms, including Agrobacterium tumefaciens, Buchnera sp., Caulobacter crescentus, Salmonella typhimurium, Salmonella typhi, Vibrio cholerae, Yersinia pestis, Haemophilus influenzae, Helicobacter pylori and Pseudomonas aeruginosa. In contrast, individual genes encoding domains I and II independently are found in Ralstonia eutropha, Neisseria meningitidis and Neisseria gonorrhoeae. In these cases, it is proposed to use the nomenclature hldA and hldC to indicate the individual kinase- and adenylyltransferase-encoding genes, respectively
rfaE encodes a bifunctional protein. It is proposed that domain I is involved in the synthesis of D-glycero-D-manno-heptose 1-phosphate, whereas domain II catalyzes the ADP transfer to form ADP-D-glycero-D-manno-heptose
HldE has highly restricted substrate specificity towards structurally modified heptose-7-phosphate analogues, substrate specificity of enzyme HldE, overview. No activity with D,L-glycero-D-manno-heptose, mannose 6-phosphate, 7-O-phosphono-L-glycero-D-manno-heptopyranosyl phosphate, and 7-O-sulfo-D-glycero-D-manno-heptopyranoside
rfaE encodes a bifunctional protein. It is proposed that domain I is involved in the synthesis of D-glycero-D-manno-heptose 1-phosphate, whereas domain II catalyzes the ADP transfer to form ADP-D-glycero-D-manno-heptose
binds to the nucleotide-binding sites without altering the overall structure of the enzyme or interfering with the binding of D-glycero-beta-D-manno-heptose-7-phosphate
binds to the nucleotide-binding sites without altering the overall structure of the enzyme or interfering with the binding of D-glycero-beta-D-manno-heptose-7-phosphate
HldE comprises two functional domains: an N-terminal region with homology to the ribokinase superfamily (HldE1 domain) and a C-terminal region with homology to the cytidylyltransferase superfamily. HldE functional unit is a dimer and structural components present in each HldE1 monomer are required for enzymatic activity
the N-terminal domain I spans amino acids 1-318 and shares structural features with members of the ribokinase family. The C-terminal domain II, which spans amino acids 344-477, has all the conserved features of the cytidylyltransferase superfamily
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structures of enzyme-substrate and enzyme-product complexes and complexes with inhibitors [[2-({[5-(2,6-dimethoxyphenyl)-1,2,4-triazin-3-yl]amino}methyl)-1,3-benzothiazol-5-yl]oxy]acetic acid and [[2-([[5-(2,6-dichlorophenyl)-1,2,4-triazin-3-yl]amino]methyl)-1,3-benzothiazol-5-yl]oxy]acetic acid. Enzyme HldA is structurally similar to members of the PfkB carbohydrate kinase family and appears to catalyze heptose phosphorylation via an in-line mechanism mediated mainly by a conserved aspartate, Asp270. Both inhibitors adopt a folded conformation and occupy the nucleotide-binding sites
development of an efficient one-pot three enzymes strategy for chemoenzymatic synthesis of ADP-D-glycero-beta-D-manno-heptose (ADP-D, D-heptose) using chemically synthesized D,D-heptose-7-phosphate and the ADP-D,D-heptose biosynthetic enzymes HldE and GmhB, method, overview
Valvano, M.A.; Marolda, C.L.; Bittner, M.; Glaskin-Clay, M.; Simon, T.L.; Klena, J.D.
The rfaE gene from Escherichia coli encodes a bifunctional protein involved in biosynthesis of the lipopolysaccharide core precursor ADP-L-glycero-D-manno-heptose
McArthur, F.; Andersson, C.E.; Loutet, S.; Mowbray, S.L.; Valvano, M.A.
Functional analysis of the glycero-manno-heptose 7-phosphate kinase domain from the bifunctional HldE protein, which is involved in ADP-L-glycero-D-manno-heptose biosynthesis
Structural-functional studies of Burkholderia cenocepacia D-glycero-beta-D-manno-heptose 7-phosphate kinase (HldA) and characterization of inhibitors with antibiotic adjuvant and antivirulence properties